This proposal is designed to perform NMR structural characterization of signaling proteins, in particular Dbl family members. The research will provide significant information on their structure-function relationships. As a first step, Bcr, a Dbl family member which has been implicated in the development of human cancer, as an NMR target- will be used to resolve the NMR solution structure of the Bcr-DH domain. This NMR structural investigation will provide critical insight into the regulation and signaling properties of Bcr, and assist us in understanding the functional properties of other Dbl family members. The NMR methodology implemented or developed during this study will be further applied to investigate Bcr-mutants and other signaling protein members.